Our previous studies have shown that several classes of heterocyclic compounds have potent pharmacological activities as antineoplastic, cytotoxic, hypoliperidemic, and antiinflammatory agents. Additional derivatives of these classes of compounds will be synthesized in order to complete a structure activity relationship (SAR) for each class of compounds and for each pharmacological activity. A number of the previously prepared derivatives were shown to possess some instability to water. Structural modifications will be made in these molecules in order to increase their stabilities and to determine if these modifications result in the retention of their potent activities. The use of molecular modeling for computer assisted drug design (CADD) will be used as a guide in the selection of the derivatives to be prepared. Quantitative structure activity relationships (QSAR) will be performed with the use of SYBYL software. The pharmacological activity testing will be carried out by Dr. Iris H. Hall at the School of Pharmacy, University of North Carolina at Chapel Hill. In addition to the SAR evaluations, the LD values, mode of action, and pharmacokinetics will be determined for each activity on the most potent agents in each chemical class. A series of 3,5-isoxazolidinediones and 3,5-pyrazolidinediones will be synthesized by the condensation of substituted malonyl chlorides and esters with hydroxamic acids, hydroxylamine, and hydrazine, respectively. The 3,5-pyrazolidinediones will be subjected to acylation and alkylation to give mono- and disubstituted derivatives. A series of 2,35- triazabicylo[3.1.0]hexane-2,4-diones will be prepared by the reaction of alkoxycarbonyl and acyl substituted diazaolkanes with 3,5- triazolinediones. The bicyclic diaziridines will be thermally ring- opened to produce 1,3,5-triazine-4,6(1H,5H)-diones. Derivatives of 2,3- dihydrol-1,4-phthalazinediones that are mono-or disubstituted at positions 2 and 3 and derivatives of 1,2-dihydro-3,6-pyridazinediones that are mono-or disubstituted at positions 1 and 2 will be prepared.